Scientific Publications

Our team of neuroscientists has authored dozens of scientific and opinion papers addressing a range of topics, from challenges in accelerating drug repurposing to evaluations of evidence surrounding dementia prevention strategies.

2015Screening for cognitive impairment in community settings yielded results consistent with expected effects of age and education. The event attracted a large proportion of individuals with memory concerns; 88.1% were told that they did not have memory problems detectable with the tests used. Further studies are needed to assess how participants respond to and use screening information, whether this information ultimately influences decision-making or outcomes, and whether memory screening programs outside healthcare settings have public health value.

2014Epidemiological projections of the prevalence of Alzheimer's disease (AD) and related dementias, the rapidly expanding population over the age of 65, and the enormous societal consequence on health, economics and community foretell of a looming global public health crisis. Currently available treatments for AD are symptomatic, with modest effect sizes and limited impact on longer term disease outcomes. There have been no newly approved pharmaceutical treatments in the last decade, despite enormous efforts to develop disease-modifying treatments directed at Alzheimer's-associated pathology. An unprecedented collaborative effort of government, regulators, industry, academia, and the community at-large is needed to address this crisis and to develop an actionable plan for rapid progress toward successfully developing effective treatments.

2014With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025.

2014The number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because randomized placebo-controlled trials (RCT) often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for Alzheimer's disease.

2014Every medical decision should be based on the best available scientific evidence. This goal motivates evidence-based medicine, a movement with undisputable value that improves the rigor of research available for medical decisions. While not the original goal of evidence-based medicine, randomized clinical trials (RCTs) have not simply become the gold standard of confidence but have overshadowed and limited the use of other sources of useful information. As stated by Kaplan et al, “over-reliance on RCTs is similar to resting all of health care evidence on a one-legged stool.”

2014Though lacking conclusive proof, decades of research suggests that specific approaches, including the consumption of coffee, may be effective in preventing age-related cognitive decline and Alzheimer's disease. Coffee and caffeine are known to enhance short-term memory and cognition, and some limited research suggests that long-term use may protect against cognitive decline or dementia.

2014Certain chronic conditions appear to be modifiable risk factors of Alzheimer's disease and related dementias. To understand the potential health and economic impacts of addressing those risk factors, we used data on a Medicare cohort to simulate four scenarios: a 10 percent reduction in the prevalence of diabetes, hypertension, cardiovascular diseases, respectively, and a 10 percent reduction in body mass index among beneficiaries who were overweight or obese. Our simulation demonstrated that reducing the prevalence of these conditions may yield "unintended benefits" by lowering the risk, delaying the onset, reducing the duration, and lowering the costs of dementia.

2014Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue of research being explored is blood based biomarkers.

2014Repurposing Food and Drug Administration (FDA)-approved drugs for a new indication may offer an accelerated pathway for new treatments but is also fraught with significant commercial, regulatory and reimbursement challenges. The Alzheimer's Drug Discovery Foundation and the Michael J. Fox Foundation for Parkinson's Research convened an advisory panel in October 2013 to better understand stakeholder perspectives related to repurposing FDA-approved drugs for neurodegerative diseases. In the resulting paper, the foundations explore opportunities for philanthropy, industry and government to begin to address these challenges, promote policy changes and develop targeted funding strategies to accelerate drug repurposing.

2013Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug's success in treating FTD may predict efficacy in more common diseases such as Alzheimer's disease. A variety of regulatory incentives, clinical features of FTD such as rapid disease progression, and relatively pure molecular pathology suggest that there are advantages to developing drugs for FTD as compared with other more common neurodegenerative diseases such as Alzheimer's disease.

2013Frontotemporal degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language, and motor phenotypes for which there are currently no effective therapies. This is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Degeneration Treatment Study Group, a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This article discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials, and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders.

2013The value of screening for cognitive impairment, including dementia and Alzheimer's disease, has been debated for decades. Recent research on causes of and treatments for cognitive impairment has converged to challenge previous thinking about screening for cognitive impairment. Consequently, changes have occurred in health care policies and priorities, including the establishment of the annual wellness visit, which requires detection of any cognitive impairment for Medicare enrollees. In response to these changes, the Alzheimer's Foundation of America and the Alzheimer's Drug Discovery Foundation convened a work group to review evidence for screening implementation and to evaluate the implications of routine dementia detection for health care redesign. The primary domains reviewed were consideration of the benefits, harms, and impact of cognitive screening on health care quality.

2013This review condenses the available scientific evidence with practical information on the available sources of long-chain omega-3 fatty acids and the research steps needed to prove their efficacy in Alzheimer's disease and related dementias.

2013This editorial provides recommendations to scientists on the process of selecting and managing a contract with an external vendor or contract research organization. Contract research organizations (CROs) are required by scientists to provide industry standard services for drug discovery and development programs. This editorial is the outcome of a one day advisory panel convened by the ADDF.

2013Individuals with Alzheimer's disease and related disorders (ADRD) have more frequent hospitalizations than individuals without ADRD, and some of these admissions may be preventable with proactive outpatient care. This study was a cross-sectional analysis of Medicare claims data from 195,024 fee-for-service ADRD beneficiaries aged ≥65 years and an equal number of matched non-ADRD controls drawn from the 5% random sample of Medicare beneficiaries in 2007-2008.

2013Increased knowledge about the biology of synaptic function has led to the development of novel cognitive-enhancing therapeutic strategies with the potential for increased efficacy and safety. This editorial highlights a diverse array of approaches currently being explored to target cognitive dysfunction due to aging and/or Alzheimer's disease.

2012Considerable knowledge has been gained from epidemiologic studies and randomized clinical trials regarding risk factors for dementia, including Alzheimer disease (AD) and vascular dementia (VaD). Most identified risk factors for dementia are similar to vascular disease risk factors for heart disease and stroke. In 2010, the National Institutes of Health Conference concluded that there are no validated modifiable factors to reduce the incidence of AD or to change its course. This research perspective specifically concerning AD disregards the fact that in community-dwelling elderly, the most common forms of dementia involve the cerebral macrovasculature and microvasculature, manifesting as VaD and mixed dementia (the combination of VaD and AD) in autopsy-confirmed cases. Thus, prevention of dementia in clinical practice should be considered from this broader and more relevant view and not just a research perspective on "pure" AD. Practicing clinicians can reasonably state to patients that, although more definitive research is clearly needed, the management and treatment of vascular disease risk factors are likely beneficial not only to prevent heart disease and stroke, but also common forms of dementia in the community.

2012This report outlines a goal-directed scientific agenda for a national initiative to overcome the Alzheimer's disease (AD) crisis. The statement, which reflects the collective views and recommendations of leaders in AD research, is intended to aid the implementation of the National Alzheimer's Project Act (NAPA)'s National Plan to defeat AD.

2012The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

2012Although the molecular mechanisms underlying the pathogenesis of Alzheimer's disease and other related neurodegenerative diseases remain unclear, accumulation of misfolded proteins, neuroinflammation, mitochondrial dysfunction and perturbed calcium homeostasis have been identified as key events leading to neuronal loss during neurodegeneration.

2012Human cognitive aging has been too long neglected and underappreciated for its critical importance to quality of life in old age. The articles in this session present novel approaches to improving cognitive function in normal aging persons with drugs and interventions that are based on findings in epidemiology, studies in aged animals, and in vitro research. In addition, since aging is the primary risk factor for Alzheimer's disease, these studies also have implications as interventions for prevention and treatment.

2011To better understand the status of frontotemporal dementia (FTD) research, and identify opportunities to accelerate translational research, we analyzed international funding for FTD and related dementias between 1998 and 2008. Search terms were compiled to define the clinical spectrum of FTD and all known mechanisms. Funders were asked to return grants that contained these search terms in the title or abstract.

2011Currently, the field is awaiting the results of several pivotal Phase III clinical Alzheimer's disease (AD) trials that target amyloid-β (Aβ). In light of the recent biomarker studies that indicate Aβ levels are at their most dynamic 5-10 years before the onset of clinical symptoms, it is becoming uncertain whether direct approaches to target Aβ will achieve desired clinical efficacy. AD is a complex neurodegenerative disease caused by dysregulation of numerous neurobiological networks and cellular functions, resulting in synaptic loss, neuronal loss, and ultimately impaired memory.

2011Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies.

2010This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia and a number of lay people, the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.

2010While Alzheimer's disease researchers continue to debate the underlying cause(s) of the disease, most agree that a diverse, multi-target approach to treatment will be necessary. To this end, the Alzheimer's Drug Discovery Foundation (ADDF) hosted its 11th International Conference on Alzheimer's Drug Discovery to highlight the array of exciting efforts from the ADDF's funded investigators.

2009Alzheimer’s disease (AD), as with other late life diseases, is undoubtedly caused by a multitude of factors that are influenced by stochastic events, an individual’s genetic makeup and environmental exposures. Combination therapy; including preventative treatments, disease modifying therapies, symptomatic agents and lifestyle changes may be our best hope at eradicating Alzheimer’s disease from our society.

2009These proceedings highlight new approaches to address and overcome the specific challenges of drug discovery for neurodegenerative diseases that were discussed at the 3rd Drug Discovery for Neurodegenerative Conference (held February 2-3, 2009 in Washington, DC). This conference was hosted by the ADDF, in partnership with the National Institutes of Health, to advance drug discovery for neurodegenerative diseases by educating scientists on the process of translating basic research into novel therapies.

2009In order to significantly tackle the most catastrophic and devastating symptom of Alzheimer's disease (AD) we must be able to detect the disease prior to the onset of clinical symptoms, and be able to offer patients preventative treatments that block or significantly slow disease progression. This review summarizes a variety of the most promising early detection methods for Alzheimer's disease (AD) and mild cognitive impairment (MCI) that could be used to identify those at high risk of developing the disease.

2008Early detection and diagnosis are critical to dementia care. However, many early cases remain undiagnosed as a result of the impracticality of neuropsychological testing, particularly in primary care. Mindstreams is an office-based computerized system for measuring cognitive function in multiple domains, with demonstrated validity, test-retest reliability, and sensitivity to treatment effects. This study evaluated its feasibility for assessment of the elderly.

2007This issue highlights advances in the field of drug discovery for Alzheimer’s disease that were discussed at the 7th International Conference on Alzheimer’s Disease Drug Discovery (held on October 12-13, 2006 in New York) following previous conferences on similar theme.

To better understand the status of frontotemporal dementia (FTD) research, and identify opportunities to accelerate translational research, we analyzed international funding for FTD and related dementias between 1998 and 2008. FTD received moderate funding over the past decade, which has decreased almost five-fold during this period. A sizable proportion of FTD funding supported mechanisms shared with Alzheimer’s disease.